Conjugated Via Claimed Linking Group, Bond, Chelating Agent, Or Coupling Agent (e.g., Conjugated To Proteinaceous Toxin Via Claimed Linking Group, Bond, Coupling Agent, Etc.) Patents (Class 424/179.1)
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Publication number: 20120308584Abstract: The invention provides protein-active agent conjugates having an amino acid motif that can be recognized by an isoprenoid transferase. The invention also provides compositions containing the conjugates, as well as methods for making the conjugates and compositions. The invention further provides methods for using the conjugates to deliver the active agent to a target cell, as well as methods for using the conjugates to treat a subject in need thereof (e.g., a subject in need of the active agent).Type: ApplicationFiled: May 8, 2012Publication date: December 6, 2012Applicant: LEGOCHEM BIOSCIENCES, INC.Inventors: Yongzu Kim, Taekyo Park, Sungho Woo, Hyangsook Lee, Sunyoung Kim, Jongun Cho, Doohwan Jung, Youngun Kim, Hyunjin Kwon, Kyuman Oh, Yunseo Chung, Yun-Hee Park
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Publication number: 20120301431Abstract: The present invention provides methods of treating (including preventing) a disease or condition associated with abnormal angiogenesis in a subject include administering a therapeutically effective amount of an AA targeting compound of the invention to the subject. The AA targeting compounds comprise AA targeting agent-linker conjugates which are linked to a combining site of an antibody.Type: ApplicationFiled: August 13, 2012Publication date: November 29, 2012Inventors: Curt Bradshaw, Abhijit Bhat, Jing Yu Lai, Venkata Doppalapudi, Dingguo Liu
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Publication number: 20120294848Abstract: The present invention relates to the provision of novel immunogens comprising an antigenic IgE peptide preferably linked to an immunogenic carrier for the prevention, treatment or alleviation of IgE-mediated disorders. The invention further relates to methods for production of these medicaments, immunogenic compositions and pharmaceutical compositing thereof and their use in medicine.Type: ApplicationFiled: August 1, 2012Publication date: November 22, 2012Applicant: PFIZER VACCINES LLCInventors: Alan Daniel Brown, Brian Robert Champion, Clare Christy, David Paul Gervais, Lyn Howard Jones, Anne Maria Kristina Kjerrstrom, David Cameron Pryde, Lee Richard Roberts, David Michael Wyatt
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Patent number: 8309094Abstract: Disclosed are anti-5T4 antibody drug conjugates and methods for preparing and using the same.Type: GrantFiled: March 30, 2012Date of Patent: November 13, 2012Assignee: Wyeth LLCInventors: Hans-Peter Gerber, John Francis DiJoseph, Kiran Manohar Khandke, Kimberly Ann Marquette, Puja Sapra, Lioudmila Gennadievna Tchistiakova
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Publication number: 20120276119Abstract: Methods of using CD37 agents, including, but not limited to, antibodies and immunoconjugates, that bind to CD37 to deplete B-cells (e.g., non-cancerous B-cells) and methods of treating autoimmune and inflammatory diseases are further provided.Type: ApplicationFiled: March 30, 2012Publication date: November 1, 2012Inventors: Jutta DECKERT, Julianto Setiady, Peter U. Park
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Patent number: 8282934Abstract: The present invention concerns methods and compositions for forming cytokine-antibody complexes using dock-and-lock technology. In preferred embodiments, the cytokine-MAb DNL complex comprises an IgG antibody attached to two AD (anchor domain) moieties and four cytokines, each attached to a DDD (docking and dimerization domain) moiety. The DDD moieties form dimers that bind to the AD moieties, resulting in a 2:1 ratio of DDD to AD. The cytokine-MAb complex exhibits improved pharmacokinetics, with a significantly longer serum half-life than either naked cytokine or PEGylated cytokine. The cytokine-MAb complex also exhibits significantly improved in vitro and in vivo efficacy compared to cytokine alone, antibody alone, unconjugated cytokine plus antibody or cytokine-MAb DNL complexes incorporating an irrelevant antibody.Type: GrantFiled: January 25, 2011Date of Patent: October 9, 2012Assignee: IBC Pharmaceuticals, Inc.Inventors: Chien-Hsing Chang, David M. Goldenberg, Edmund A. Rossi
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Patent number: 8268317Abstract: The invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a camptothecin as a therapeutic moiety, and further relates to processes for making and using the said conjugates.Type: GrantFiled: August 11, 2009Date of Patent: September 18, 2012Assignee: Immunomedics, Inc.Inventors: Serengulam V. Govindan, David M. Goldenberg, Sung-Ju Moon
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Patent number: 8268319Abstract: The invention relates to therapeutic conjugates with improved ability to target various cancer cells containing a targeting moiety and a therapeutic moiety. The targeting and therapeutic moieties are linked via an acid cleavable linkage that increases therapeutic efficacy of the immunoconjugate.Type: GrantFiled: July 30, 2009Date of Patent: September 18, 2012Assignee: Immunomedics, Inc.Inventor: Serengulam V. Govindan
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Publication number: 20120225089Abstract: Provided herein are cryptophycin conjugates and compositions containing them. Methods of making and using such compounds also are provided.Type: ApplicationFiled: December 20, 2011Publication date: September 6, 2012Applicant: SANOFIInventors: Hervé BOUCHARD, Marie-Priscille BRUN, Alain COMMERCON, Jidong ZHANG
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Patent number: 8252902Abstract: The present invention provides antibody targeting compounds in which the specificity of the antibody has been reprogrammed by covalently or noncovalently linking a targeting agent to the combining site of an antibody. By this approach, the covalently modified antibody takes on the binding specificity of the targeting agent. The compound may have biological activity provided by the targeting agent or by a separate biological agent. Various uses of the invention compounds are provided.Type: GrantFiled: October 22, 2002Date of Patent: August 28, 2012Assignee: The Scripps Research InstituteInventors: Carlos F. Barbas, Christoph Rader, Subhash C. Sinha, Richard A. Lerner
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Patent number: 8226945Abstract: Anti-CD22 antibodies and immunoconjugates thereof are provided. Methods of using anti-CD22 antibodies and immunoconjugates thereof are provided.Type: GrantFiled: November 4, 2010Date of Patent: July 24, 2012Assignee: Genentech, Inc.Inventors: Allen J. Ebens, Jr., Alane M. Gray, Wei-Ching Liang, Yan Wu, Shang-Fan Yu
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Publication number: 20120148610Abstract: Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo.Type: ApplicationFiled: February 15, 2012Publication date: June 14, 2012Applicant: Seattle Genetics, Inc.Inventors: Svetlana O. Doronina, Peter D. Senter, Brian E. Toki, Allen J. Ebens, Toni Beth Kline, Paul Polakis, Mark X. Sliwkowski, Susan D. Spencer
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Patent number: 8197847Abstract: The application discloses a process for making a polymer having pendant side groups comprising: (i) polymerising an olefinically unsaturated monomer functionalized with (a) an azide group optionally protected by a protecting group, or (b) an alkyne group optionally protected by a protecting group, by living radical polymerization, most preferably RAFT, transitional metal mediated living radical polymerization (TMM-LRP) and/or atom transfer radical polymerization, to produce a polymer intermediate; (ii) removing, when present, at least a portion of the total number of protecting groups from the polymer intermediate; (iii) reacting the polymer intermediate with at least one pendant side group moiety functionalised with (a) an alkyne group or (b) an azide group respectively so that the alkyne and azide groups react to attach the pendant side group to the polymer. Processes for making supports comprising pendant side groups, and polymers and supports prepared by the method are also disclosed.Type: GrantFiled: September 5, 2008Date of Patent: June 12, 2012Assignee: Warwick Effect Polymers Ltd.Inventors: David M. Haddleton, Guiseppe Mantovani, Vincent Ladmiral
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Publication number: 20120141507Abstract: Methods of making ligand-decorated polymer conjugates of therapeutic glycoproteins are described. Improved targeting of glycoproteins to specific tissues is achieved by masking the natural carbohydrate and other surface determinants with high molecular weight polymers, such as, e.g., PEG, polysialic acid, etc., which in turn are decorated with target-specific ligands. In some embodiments, acid-labile linkages in such conjugates or rapidly degradable masking groups allow for the intracellular release of the polymer from the glycoprotein, for example, under conditions found in lysosomes.Type: ApplicationFiled: January 20, 2012Publication date: June 7, 2012Inventor: James Stefano
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Publication number: 20120141508Abstract: Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo.Type: ApplicationFiled: February 15, 2012Publication date: June 7, 2012Applicant: Seattle Genetics, Inc.Inventors: Svetlana O. Doronina, Peter D. Senter, Brian E. Toki, Allen J. Ebens, Toni Beth Kline, Paul Polakis, Mark X. Sliwkowski, Susan D. Spencer
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Publication number: 20120141509Abstract: Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo.Type: ApplicationFiled: February 15, 2012Publication date: June 7, 2012Applicant: Seattle Genetics, Inc.Inventors: Svetlana O. Doronina, Peter D. Senter, Brian E. Toki, Allen J. Ebens, Toni Beth Kline, Paul Polakis, Mark X. Sliwkowski, Susan D. Spencer
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Patent number: 8192743Abstract: Activated polymeric bicine derivatives such as, as well as conjugates made therewith are disclosed. Methods of making and using the bicine derivatives are also disclosed.Type: GrantFiled: July 25, 2008Date of Patent: June 5, 2012Assignee: Enzon Pharmaceuticals, Inc.Inventors: Hong Zhao, Richard B. Greenwald, Susan L. Adler, legal representative
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Publication number: 20120114704Abstract: The present invention provides antibodies or antigen-binding fragments thereof that specifically hind the ENDO180 polypeptide and are internalized thereby, to conjugates comprising the molecules, to compositions comprising the antibodies and conjugates and to methods of using the same for delivery of therapeutic agents to cells that express the ENDO180 polypeptide on the surface of the cell for treating cell proliferative diseases or disorders and fibrosis, and for controlling (modulating) tumor progression.Type: ApplicationFiled: March 23, 2010Publication date: May 10, 2012Inventor: Elena Feinstein
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Patent number: 8153114Abstract: The present invention relates to new and improved interleukin-7 polypeptides, as well as compositions comprising the same, their preparation and uses. The invention more particularly relates to hyperglycosylated IL-7 polypeptides having improved properties, as well as their manufacture and therapeutic uses. The invention also discloses novel IL-7 polypeptides having modified amino acid sequences containing artificially created glycosylation site(s), as well as corresponding nucleic acid molecules, vectors and recombinant host cells. The invention also relates to the use of such polypeptides, cells or nucleic acids for curative or preventive treatment of mammalian subjects, including human subjects.Type: GrantFiled: August 24, 2011Date of Patent: April 10, 2012Assignee: CytherisInventors: Michel Morre, Brigitte Assouline, Iann Rance, Anne Gregoire, Corinne Breque
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Patent number: 8142781Abstract: The invention provides compositions, methods, and kits for increasing transport of agents across the blood brain barrier while allowing their activity once across the barrier to remain substantially intact. The agents are transported across the blood brain barrier via one or more endogenous receptor-mediated transport systems. In some embodiments the agents are therapeutic, diagnostic, or research agents.Type: GrantFiled: October 7, 2005Date of Patent: March 27, 2012Assignee: ArmaGen Technologies, Inc.Inventors: William M. Pardridge, Ruben J. Boado
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Patent number: 8124094Abstract: Disclosed are an Fc fragment modified by a non-peptide polymer, a pharmaceutical composition comprising the Fc fragment modified by the non-peptide polymer as a carrier, a complex of the Fc fragment and a drug via a linker and a pharmaceutical composition comprising such a complex. The Fc fragment modified by a non-peptide peptide according to the present invention lacks immunogenicity and effector functions. Due to these properties, the Fc fragment maintains the in vivo activity of a drug conjugated thereto in high levels, remarkably increases the serum half-life of the drug, and remarkably reduces the risk of inducing immune responses.Type: GrantFiled: April 28, 2005Date of Patent: February 28, 2012Assignee: Hanmi Holdings Co., Ltd.Inventors: Young Min Kim, Sung Min Bae, Dae Jin Kim, Dae Hae Song, Chang Ki Lim, Se Chang Kwon, Gwan Sun Lee
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Patent number: 8124073Abstract: Methods of making ligand-decorated polymer conjugates of therapeutic glycoproteins are described. Improved targeting of glycoproteins to specific tissues is achieved by masking the natural carbohydrate and other surface determinants with high molecular weight polymers, such as, e.g., PEG, polysialic acid, etc., which in turn are decorated with target-specific ligands. In some embodiments, acid-labile linkages in such conjugates or rapidly degradable masking groups allow for the intracellular release of the polymer from the glycoprotein, for example, under conditions found in lysosomes.Type: GrantFiled: January 8, 2008Date of Patent: February 28, 2012Assignee: Genzyme CorporationInventor: James Stefano
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Patent number: 8119101Abstract: Disclosed are compositions that include anti-CD74 immunoconjugates and optionally a therapeutic and/or diagnostic agent. In preferred embodiments, the immunoconjugates comprise one or more anti-CD74 antibodies or antigen-binding fragments thereof, conjugated to a liposome or micelle. Also disclosed are methods for preparing the immunoconjugates and using the immunoconjugates in diagnostic and therapeutic procedures. In certain preferred embodiments, the therapeutic methods comprise administering to a subject with a CD74-expressing disease an anti-CD74 immunoconjugate and thereby inducing apoptosis of CD74-expressing cells. In more preferred embodiments, the CD74 immunoconjugate is capable of inducing cell death in the absence of any other therapeutic agent, although such agents may be optionally administered prior to, together with or subsequent to administration of the anti-CD74 immunoconjugate. The compositions may be part of a kit for administering the anti-CD74 immunoconjugates or compositions.Type: GrantFiled: May 28, 2010Date of Patent: February 21, 2012Assignees: The Ohio State University, Immunomedics, Inc.Inventors: John C. Byrd, David M. Goldenberg, Hans J. Hansen
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Publication number: 20120034245Abstract: Multivalent binding peptides, including bi-specific binding peptides, having immunoglobulin effector function are provided, along with encoding nucleic acids, vectors and host cells as well as methods for making such peptides and methods for using such peptides to treat or prevent a variety of diseases, disorders or conditions, as well as to ameliorate at least one symptom associated with such a disease, disorder or condition.Type: ApplicationFiled: June 12, 2007Publication date: February 9, 2012Applicant: Emergent Product Development Seattle, LLCInventors: Peter Armstrong Thompson, Jeffrey A. Ledbetter, Martha Susan Hayden-Ledbetter, Laura Sue Grosmaire, Robert Bader, William Brady
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Publication number: 20120034246Abstract: Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo.Type: ApplicationFiled: April 19, 2011Publication date: February 9, 2012Applicant: SEATTLE GENETICS, INC.Inventors: SVETLANA O. DORONINA, PETER D. SENTER, BRIAN E. TOKI, ALLEN J. EBENS, TONI BETH KLINE, PAUL POLAKIS, MARK X. SLIWKOWSKI, SUSAN D. SPENCER
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Publication number: 20120034247Abstract: Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo.Type: ApplicationFiled: July 22, 2011Publication date: February 9, 2012Applicant: Seattle Genetics, Inc.Inventors: Svetlana O. Doronina, Peter D. Senter, Brian E. Toki, Allen J. Ebens, Toni Beth Kline, Paul Polakis, Mark X. Sliwkowski, Susan D. Spencer
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Publication number: 20120014975Abstract: The invention relates to modified single domain antigen binding molecules, e.g., SDAB molecules, in particular TNF?-binding SDAB molecules. Method of preparing, and using the modified single domain antigen binding molecules described herein, to treat, e.g., TNF?-associated disorders, are also disclosed.Type: ApplicationFiled: July 14, 2011Publication date: January 19, 2012Applicant: Wyeth LLCInventors: Martin Hegen, Stephane Hubert Olland, Yulia Vugmeyster, Xin Xu
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Publication number: 20120009181Abstract: Novel anti-cancer agents, including, but not limited to, antibodies and immunoconjugates, that bind to human folate receptor 1 are provided. Methods of using the agents, antibodies, or immunoconjugates, such as methods of inhibiting tumor growth are further provided.Type: ApplicationFiled: February 24, 2011Publication date: January 12, 2012Inventors: Olga AB, Daniel TAVARES, Lingyun RUI, Gillian PAYNE, Viktor S. GOLDMAKHER
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Publication number: 20120003248Abstract: Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo.Type: ApplicationFiled: April 29, 2011Publication date: January 5, 2012Applicant: Seattle Genetics, Inc.Inventors: Svetlana O. Doronina, Peter D. Senter, Brian E. Toki, Allen J. Ebens, Toni Beth Kline, Paul Polakis, Mark X. Sliwkowski, Susan D. Spencer
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Publication number: 20120003247Abstract: Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo.Type: ApplicationFiled: April 29, 2011Publication date: January 5, 2012Applicant: Seattle Genetics, Inc.Inventors: Svetlana O. Doronina, Peter D. Senter, Brian E. Toki
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Publication number: 20120004643Abstract: The present invention includes compositions and methods for increasing the effectiveness of antigen presentation using a DCIR-specific antibody or fragment thereof to which an antigen is attached that forms an antibody-antigen complex, wherein the antigen is processed and presented by a dendritic cell that has been contacted with the antibody-antigen complex.Type: ApplicationFiled: September 16, 2011Publication date: January 5, 2012Applicant: BAYLOR RESEARCH INSTITUTEInventors: Gerard Zurawski, Jacques Banchereau, Eynav Klechevsky, Sandra Zurawski, Anne-Laure Flamar
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Publication number: 20120003249Abstract: An immuno-molecule which comprises a soluble human MHC class I effector domain; and an antibody targeting domain which is linked to the soluble human MHC class I effector domain, methods of making same and uses thereof.Type: ApplicationFiled: September 19, 2011Publication date: January 5, 2012Applicants: Teva Pharmaceutical Industries Ltd., Technion Research & Development Foundation Ltd.Inventors: Yoram REITER, Avital Lev
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Patent number: 8088387Abstract: The present invention discloses a method for targeting maytansinoids to a selected cell population, the method comprising contacting a cell population or tissue suspected of containing the selected cell population with a cell-binding agent maytansinoid conjugate, wherein one or more maytansinoids is covalently linked to the cell-binding agent via a non-cleavable linker and the cell-binding agent binds to cells of the selected cell population.Type: GrantFiled: October 8, 2004Date of Patent: January 3, 2012Assignee: Immunogen Inc.Inventors: Rita M. Steeves, Ravi V. J. Chari, Walter A. Blättler
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Patent number: 8088884Abstract: The present disclosure provides novel POZ-2 derivatives, methods for synthesizing POZ-2 derivatives and intermediates useful in such methods. In one embodiment, the POZ-2 derivative comprises two linear POZ chains of the present disclosure linked directly or indirectly to a branching moiety that contains a functional group for linking the POZ-2 derivative to the target molecule. Target molecule-POZ-2 conjugates are also described. In certain embodiment, the POZ-2 derivatives have low polydispersity values and a decreased amount of impurities produced by unwanted side reactions, such as, but not limited to, chain transfer.Type: GrantFiled: September 29, 2008Date of Patent: January 3, 2012Assignee: Serina Therapeutics, Inc.Inventors: J. Milton Harris, Michael David Bentley, Kunsang Yoon, Zhihao Fang
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Publication number: 20110318306Abstract: The present invention concerns methods and compositions for forming cytokine-antibody complexes using dock-and-lock technology. In preferred embodiments, the cytokine-MAb DNL complex comprises an IgG antibody attached to two AD (anchor domain) moieties and four cytokines, each attached to a DDD (docking and dimerization domain) moiety. The DDD moieties form dimers that bind to the AD moieties, resulting in a 2:1 ratio of DDD to AD. The cytokine-MAb complex exhibits improved pharmacokinetics, with a significantly longer serum half-life than either naked cytokine or PEGylated cytokine. The cytokine-MAb complex also exhibits significantly improved in vitro and in vivo efficacy compared to cytokine alone, antibody alone, unconjugated cytokine plus antibody or cytokine-MAb DNL complexes incorporating an irrelevant antibody.Type: ApplicationFiled: January 25, 2011Publication date: December 29, 2011Applicant: IBC PHARMACEUTICALS, INC.Inventors: Chien-Hsing Chang, David M. Goldenberg, Edmund A. Rossi
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Publication number: 20110300131Abstract: The application provides methods of diagnosis, prognosis, prophylaxis and treatment of ovarian, pancreatic and other cancers using antibodies that specifically bind to denatured CD70.Type: ApplicationFiled: April 10, 2009Publication date: December 8, 2011Applicant: SEATTLE GENETICS, INC.Inventors: Maureen Ryan, Maria Leia Smith
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Patent number: 8067006Abstract: The present invention concerns methods and compositions for delivery of therapeutic agents to target cells, tissues or organisms. In preferred embodiments, the therapeutic agents are delivered in the form of therapeutic-loaded polymers that may comprise many copies of one or more therapeutic agents. In more preferred embodiments, the polymer may be conjugated to a peptide moiety that contains one or more haptens, such as HSG. The agent-polymer-peptide complex may be delivered to target cells by, for example, a pre-targeting technique utilizing bispecific or multispecific antibodies or fragments, having at least one binding arm that recognizes the hapten and at least a second binding arm that binds specifically to a disease or pathogen associated antigen, such as a tumor associated antigen. Methods for synthesizing and using such therapeutic-loaded polymers and their conjugates are provided.Type: GrantFiled: April 23, 2010Date of Patent: November 29, 2011Assignee: Immunomedics, Inc.Inventors: Serengulam V. Govindan, Sung-Ju Moon, David M. Goldenberg, Chien-Hsing Chang
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Patent number: 8067005Abstract: Divalent antibody fragments are described, each of which has one or more interchain bridges containing a synthetic or naturally occurring polymer selected from a polyalkylene, polyakenylene, polyoxyalkylene or polysaccharide. Each bridge may be the residue of a homo- or heterobifunctional cross-linking reagent and serves to link two heavy chains in each antibody fragment via the sulphur atoms of cysteine residues present in the chains. Each fragment may be attached to one or more effector or reporter molecules, and is of use in therapy or diagnostics where it has markedly improved binding and/or pharmacokinetic properties when compared to other antibody fragments which have the same number and type of polymer molecules but in which the polymer molecules are randomly attached.Type: GrantFiled: June 8, 1999Date of Patent: November 29, 2011Assignee: UCB Pharma S.A.Inventors: Andrew Paul Chapman, David John King
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Patent number: 8057798Abstract: The present invention includes compositions and methods for increasing the effectiveness of antigen presentation using a DCIR-specific antibody or fragment thereof to which an antigen is attached that forms an antibody-antigen complex, wherein the antigen is processed and presented by a dendritic cell that has been contacted with the antibody-antigen complex.Type: GrantFiled: February 1, 2008Date of Patent: November 15, 2011Assignee: Baylor Research InstituteInventors: Gerald Zurawski, Jacques F. Banchereau, Eynav Klechevsky, Sandra Zurawski, Anne-Laure Flamar
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Publication number: 20110274704Abstract: The present invention concerns methods and compositions for forming immunotoxin complexes having a high efficacy and low systemic toxicity. In preferred embodiments, the toxin moiety is a ranpirnase (Rap), such as Rap(Q). In more preferred embodiments, the immunotoxin is made using dock-and-lock (DNL) technology. The immunotoxin exhibits improved pharmacokinetics, with a longer serum half-life and significantly greater efficacy compared to toxin alone, antibody alone, unconjugated toxin plus antibody or even other types of toxin-antibody constructs. In a most preferred embodiment the construct comprises an anti-Trop-2 antibody conjugated to Rap, although other combinations of antibodies, antibody fragments and toxins may be used to form the subject immunotoxins. The immunotoxins are of use to treat a variety of diseases, such as cancer, autoimmune disease or immune dysfunction.Type: ApplicationFiled: August 30, 2010Publication date: November 10, 2011Applicants: IBC PHARMACEUTICALS, INC., IMMUNOMEDICS, INC.Inventors: Chien-Hsing Chang, David M. Goldenberg, Edmund A. Rossi
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Publication number: 20110274705Abstract: The present invention is directed to novel compositions that cause effective redirection of class I-immunity to Tc1 effectors, that take advantage of the unexpected loading of MHC I by peptide within IgG backbone combined with appropriate instruction of antigen presenting cells. Such compositions are able to transform a seemingly ineffective therapeutics into a highly effective one, associated with generation of class I-restricted cytolytic cells and IFN-?, IL-2 producing T cells, further associated with protection against a highly virulent microbe or recovery from malignant tumoral process.Type: ApplicationFiled: April 1, 2011Publication date: November 10, 2011Inventors: Adrian Bot, Lilin Wang, Dan Smith, Bill Phillips
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Publication number: 20110250130Abstract: Isolated binding proteins, e.g., antibodies or antigen binding portions thereof, which bind to tumor necrosis factor-alpha (TNF-?), e.g., human TNF-?, and related antibody-based compositions and molecules are disclosed. Also disclosed are pharmaceutical compositions comprising the antibodies, as well as therapeutic and diagnostic methods for using the antibodies.Type: ApplicationFiled: April 6, 2011Publication date: October 13, 2011Inventors: Lorenzo Benatuil, Tariq Ghayur, Carrie L. Goodreau, Peter C. Isakson, Jochen Salfeld
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Patent number: 8034959Abstract: The present invention provides analogues of duocarmycins that are potent cytotoxins. Also provided are peptidyl and disulfide linkers that are cleaved in vivo. The linkers are of use in forming prodrugs and conjugates of the cytotoxins of the invention as well as other diagnostic and therapeutic moieties. The invention provides prodrugs and conjugates of the duocarmycin analogues with the linker arms of the invention.Type: GrantFiled: March 2, 2009Date of Patent: October 11, 2011Assignee: Medarex, Inc.Inventors: Howard P. Ng, Zhi-Hong Li, Danny P. C. McGee, Oliver L. Saunders, Guoxian Wu, David John King, Valeri Martichonok, Sharon Elaine Boyd, Thomas J. Lobl
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Patent number: 8034352Abstract: The present invention concerns methods and compositions for forming cytokine-antibody complexes using dock-and-lock technology. In preferred embodiments, the cytokine-MAb DNL complex comprises an IgG antibody attached to two AD (anchor domain) moieties and four cytokines, each attached to a DDD (docking and dimerization domain) moiety. The DDD moieties form dimers that bind to the AD moieties, resulting in a 2:1 ratio of DDD to AD. The cytokine-MAb complex exhibits improved pharmacokinetics, with a significantly longer serum half-life than either naked cytokine or PEGylated cytokine. The cytokine-MAb complex also exhibits significantly improved in vitro and in vivo efficacy compared to cytokine alone, antibody alone, unconjugated cytokine plus antibody or cytokine-MAb DNL complexes incorporating an irrelevant antibody. In more preferred embodiment the cytokine is G-CSF, erythropoietin or INF-?2b.Type: GrantFiled: April 1, 2010Date of Patent: October 11, 2011Assignee: IBC Pharmaceuticals, Inc.Inventors: Chien-Hsing Chang, David M. Goldenberg, Edmund A. Rossi
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Publication number: 20110236309Abstract: The invention provides hetero-multivalent ligand binging agents (traps) for members of the TGF-? superfamily, as well as methods for making and using such constructs. In an embodiment of the invention there is provided a hetero-multivalent binding agent with affinity for a member of the TGF-? superfamily, said agent comprising the general structure (I): (<bd1>-linker1)k-[{<bd1>-linker2-<bd2>-linker3r-}n-(<bd3>)m-(linker4-<bd4>)d]h, where bd1, bd2, bd3 and bd4 are polypeptide binding domains having an affinity for different sites on the same member or for different members of the TGF-? superfamily, wherein at least two of bd1, bd2, bd3, and bd4 are different from each other.Type: ApplicationFiled: September 17, 2009Publication date: September 29, 2011Inventors: Maureen D. O'Connor-Mccourt, Traian Sulea, John C. Zwaagstra, Jason Baardsnes, Catherine Collins
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Patent number: 7994135Abstract: Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo.Type: GrantFiled: August 3, 2007Date of Patent: August 9, 2011Assignee: Seattle Genetics, Inc.Inventors: Svetlana O. Doronina, Peter D. Senter, Brian E. Toki, Allen J. Ebens, Toni Beth Kline, Paul Polakis, Mark X. Sliwkowski, Susan D. Spencer
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Patent number: 7989554Abstract: A new method of preparing a tertiary alkyl ester of a polyalkylene oxide is provided. The new method employs milder conditions that avoid the back reaction to the starting polyalkylene oxide. The tertiary alkyl ester of a polyalkylene oxide is then reacted with a suitable acid to produce a polyalkylene oxide acid.Type: GrantFiled: January 10, 2006Date of Patent: August 2, 2011Assignee: Enzon Pharmaceuticals, Inc.Inventors: Hong Zhao, Anthony J. Martinez
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Patent number: 7989594Abstract: The present invention provides antibody Fab fragments in which the heavy chain constant region terminates at the interchain cysteine of CH1. Also provided are antibody Fab fragments in which the heavy chain constant region terminates at the interchain cysteine of CH1 to which one or more effector molecules are attached.Type: GrantFiled: July 1, 2004Date of Patent: August 2, 2011Assignee: Celltech R & D LimitedInventors: David Paul Humphreys, Sam Philip Heywood
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Publication number: 20110177103Abstract: The present invention is directed to compositions of matter useful for the diagnosis and treatment of tumor in mammals and to methods of using those compositions of matter for the same.Type: ApplicationFiled: March 11, 2011Publication date: July 21, 2011Inventors: Mark S. Dennis, William Mallet, Paul Polakis
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Patent number: 7977464Abstract: There is disclosed antibody molecules containing at least one CDR derived from a mouse monoclonal antibody having specificity for human TNF?. There is also disclosed a CDR grafted antibody wherein at least one of the CDRs is a hybrid CDR. Further disclosed are DNA sequences encoding the chains of the antibody molecules, vectors, transformed host cells and uses of the antibody molecules in the treatment of diseases mediated by TNF?.Type: GrantFiled: June 18, 2008Date of Patent: July 12, 2011Assignee: UCB Pharma S.A.Inventors: Diljeet Singh Athwal, Derek Thomas Brown, Andrew Neil Charles Weir, Andrew George Popplewell, Andrew Paul Chapman, David John King